The FDA’s Advisory Committee meeting is scheduled for September 27, 2023, and the PDUFA date for the company’s BLA review is set for December 8, 2023.
The FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee will review the supporting data of the biologics license application (BLA) for BrainStorm Cell Therapeutics’ NurOwn, an investigational autologous mesenchymal stem cell (MSC) neurotrophic factor–secreting cell therapy product intended to treat amyotrophic lateral sclerosis (ALS), in an advisory committee (AdComm) meeting on September 27, 2023, according to an announcement.1 In addition, the Prescription Drug User Fee Act (PDUFA) action date for the BLA has been set by the agency for December 8, 2023.
The AdComm meeting was previously noted to be confirmed without a scheduled date in a March 2023 statement from BrainStorm.2 The company originally filed a BLA for the cell therapy in September 2022, in spite of FDA feedback received in February 2021 that recommended against filing based on a summary of high-level data from the pivotal phase 3 clinical trial (NCT03280056) that evaluated the treatment in patients with ALS.1,3 In November 2022, the FDA sent the company a refusal to file letter regarding the BLA, but also indicated that it would allow for a type A meeting to discuss the letter’s content.4 BrainStorm requested the type A meeting, which took place on January 11, 2023.2 After this meeting and several additional discussions with the agency, the company requested use of the FDA's "File Over Protest" procedure to move the regulatory process forward.1 As a result, on February 7, 2023, the FDA continued its review of the BLA.
"We are encouraged by the regulatory flexibility that the FDA has shown over the last year in ALS broadly, and with respect to NurOwn in particular, and believe an Advisory Committee meeting is good for patients," Chaim Lebovits, the co-CEO and president of BrainStorm Cell Therapeutics, said in a June 6, 2023, statement.1 "We are of course deeply committed to the scientific and regulatory process, which includes continuing research to confirm the results of the NurOwn clinical program and are working with ALS experts in designing a rigorous clinical study to answer important questions about this therapy and inform further research on ALS."
In March 2023, at the time of the initial announcement of the upcoming AdComm meeting, CGTLive™ spoke with Stacy Lindborg, PhD, the co-CEO of BrainStorm Cell Therapeutics, about NurOwn and the clinical data that have been generated in trials so far. She noted that of particular importance for the upcoming AdComm meeting is the floor effect of the ALS Functional Rating Scale—the scale cannot measure disease progression after a certain point in patients with advanced ALS.
“FDA flexibility is good for patients in these fatal illnesses and these rapidly progressing illnesses, such as ALS,” Lindborg said in the interview. “It's good for science, as it allows us to learn more rapidly as a community in ALS drug development. We are confident in the effectiveness of NurOwn and we're grateful to the FDA for the opportunity to review the full body of clinical evidence.”
BrainStorm has stated that the floor effect is likely the reason that the phase 3 trial did not achieve statistically significant results for its primary and secondary end points,1 and the company has continued to push forward with the regulatory process in light of other evidence of clinical benefit. Brainstorm noted that in a prespecified subgroup of patients with less advanced disease, who had a score of at least 35 on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), a statistically significant difference in the change from baseline in ALSFRS-R was observed favoring the group of patients who received NurOwn compared with the group of patients who received a placebo. A posthoc sensitivity analysis of patients who had an ALSFFRS-R score of 26 or higher also found that participants treated with NurOwn progressed 2 points less on the ALSFRS-R scale on average compared with patients who received the placebo.
"We welcome the opportunity to present our data at the forthcoming AdComm,” Lindborg added to the June 6 statement.“ We remain confident in NurOwn and believe our data support regulatory approval. As is the case with most ALS research, our clinical program generated complex results, which deserve a thoughtful and holistic review by scientists, ALS experts, FDA reviewers, advocates, and patients. We believe this approach honors the needs of those living with ALS and offers the greatest promise for BrainStorm to fulfill our commitment to the ALS community."